The broad objectives of these proposed studies are: 1) to investigate the enzyme system which metabolizes the volatile anesthetics and 2) to explore the possibility that intermediates produced in the course of this metabolism can lead to toxic side effects if in large enough concentration, and 3) to determine if possible the mechanism leading to cell death as a result of the intoxication of the cell with a foreign drug. The enzyme systems which catalyze the biotransformation of volatile anesthetics will be studied in vitro in perfused rat livers, hepatocytes, microsomal fractions, and partially purified cytochrome P-450. Other studies will be carried out to identify the metabolic products of these biotransformations, and to determine if there are species differences in these pathways. The liver samples will be apparently normal in all respects and free of anesthetics and other drugs at the time of use. However, some effort will be put forth to determine which physiological alterations imposed in vivo or in vitro interfere with or alter the pathway of metabolism. Additional studies will be performed to determine the mechanisms of biotransformation. A better understanding of the biotransformation of volatile anesthetic agents could be very important in explaining some of the unexpected and sometimes lethal reactions observed in clinical anesthesia.